A series of lipophilic, phosphorus based nucleotide prodrugs with antiviral activity against the AIDS virus, hepatitis B and herpes virus will be synthesized and tested in vitro and in vivo. These prodrugs will be synthesized by employing a novel phosphorus prodrug technology developed by Drug Innovation and Design Inc. The prodrugs are designed to be absorbed following oral administration and to passively diffuse into all tissues including the brain. The prodrugs will undergo transformation to the parent phosphate or phosphonate drug by a novel elimination reaction. It is anticipated that this work will lead to the rapid development of several clinically useful drugs for the treatment of life threatening viral infections.